Precursor-Directed Diversification of Cyclic Tetrapeptidic Pseudoxylallemycins

Abstract

Cyclic peptides containing non-proteinogenic amino acids often exhibit a broad bioactivity spectrum and many have entered clinical trials with good prospects for drug development. We recently reported the discovery of six cyclic tetrapeptides, pseudoxylallemycins A-F (1-6), from a termite-associated Pseudoxylaria sp. X802. These compounds contain a rare O-homoallenyl-l-tyrosine moiety and show promising antimicrobial activity against the Gram-negative pathogenic bacterium Pseudomonas aeruginosa. To perform more detailed structure-activity studies, we pursued a precursor-directed diversification strategy. Herein, we report the purification, identification, and testing of 21 new pseudoxylallemycin derivatives.

Keywords: allenes; amino acids; bioactivity; natural products; peptides; synthases.